Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study

Souied, Eric H; Devin, François; Mauget-Faÿsse, Martine; Kolář, Petr; Wolf-Schnurrbusch, Ute; Framme, Carsten Karl Josef; Gaucher, David; Querques, Giuseppe; Stumpp, Michael T; Wolf, Sebastian (2014). Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study. American journal of ophthalmology, 158(4), 724-732.e2. Elsevier Science 10.1016/j.ajo.2014.05.037

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PURPOSE To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN Phase I/II, open-label, multicenter, dose-escalation study. METHODS Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Wolf-Schnurrbusch, Ute; Framme, Carsten Karl Josef and Wolf, Sebastian

Subjects:

600 Technology > 610 Medicine & health
500 Science

ISSN:

0002-9394

Publisher:

Elsevier Science

Language:

English

Submitter:

Sebastian Wolf

Date Deposited:

18 Mar 2015 11:06

Last Modified:

19 Mar 2015 22:32

Publisher DOI:

10.1016/j.ajo.2014.05.037

PubMed ID:

24907435

BORIS DOI:

10.7892/boris.64684

URI:

https://boris.unibe.ch/id/eprint/64684

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